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B32PAI - Pharmaceutics > Emulsion and Suspension Stability > Flashcards

Emulsion and Suspension Stability Flashcards

1
Q

What is a colloid?

A

A disperse system in which one phase is in the form of tiny particles or droplets

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2
Q

Why are dispersed systems used for hydrophobic drugs?

A
  • Cannot be dissolved in water
  • Dissolved in oil instead
  • Oil is dispersed in water (isotonic) to form an emulsion
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3
Q

What stabilises emulsions?

A

Polymer/surfactant sits at interphase e.g. molecular film on oil droplets

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4
Q

How large are droplets in emulsions?

A

From 10μm for coarse systems to less than 200nm for fine emulsions

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5
Q

What process does an emulsifier stop?

A
  • The re-separation of oil and water to OG low energy system
  • Emulsion requires large amount of energy to create large amount of new surface; dispersed emulsion has a higher energy than unmixed oil and water so will revert back
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6
Q

How do emulsions keep droplets apart?

A

The surfactant (emulsifier) forms a charged layer around the droplet at the interphase; repulsion of similar charges yields a stable emulsion

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7
Q

What applications are there for emulsions?

A

Intravenous:

  • Total Parenteral Nutrition; administration of fats as intralipid, feeding emulsion simulates chylomicrons
  • Delivery of hydrophobic drugs

Oral:

  • Fats; enteric feeds
  • Delivery of hydrophobic drugs

Intramuscular:

  • W/O emulsions for sustained release
  • Emulsion vaccine adjuvants
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8
Q

What excipients are acceptable for emulsion use?

A

IV:
- Oil phase; soya bean oil/medium chain triglyceridies

Emulsifiers:

  • Phospholipids (must be purified; some components toxic e.g. phosphatidylinositol) from egg yolk or soya beans
  • Hydrophilic Pluronics (non-ionic surfactants)
  • Polysorbate/bile salts in small volume parentals

IM:

  • Sesame oil
  • Squalane and Pluronic L121 in Syntex Adjuvant Formulation (designed to induce immune response)
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9
Q

How are hydrophobic oil-soluble drugs incorporated into emulsions?

A

Dissolved in oil which is then emulsified; drug must be v. hydrophobic (Log P > 5) or drug will transfer through aqueous phase and crystallise out

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10
Q

What are surface active drugs and how can they be incorporated?

A
  • One part hydrophilic, one part hydrophilic

- Absorbed at the interphase

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11
Q

What happens in flocculation? What does it mean for the disperse system?

A
  • Particles/droplets cluster together in an open structure
  • They maintain their individual identity though
  • Can be redispersed to single particles/droplets by shaking
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12
Q

What is coagulation/aggregation and what does this mean for the disperse system?

A
  • Small aggregates form
  • Surface area is decreased so surface tension is experienced by fewer molecules
  • Attractive forces between particles very strong
  • Cannot be redispersed to single particles by shaking; permanent failure of medicine
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13
Q

What is coalescence and what are its consequences for a disperse system?

A
  • ‘Sedimentation’
  • Droplet structure lost entirely
  • Impossible to reform emulsion
  • Total failure
  • AKA ‘cracking’
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14
Q

What forces are acting on particles in disperse systems?

A
  • Particles of less than 2 microns diameter are constantly moving due to Brownian motion
  • Kinetic energy depends on temperature and shaking etc.
  • Particles experience repulsion due to electrostatic interactions
  • Particles also experience attraction due to vdWs
  • Steric forces exhibited if they have a non-ionic surfactant coating them (steric hindrance)
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15
Q

What is the DVLO theory?

A

Theory of balance between electrostatic repulsion and attractive forces.

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16
Q

What does the attractive force/vdW (Va) between particles depend on?

A
  • Particle radius

- Particle separation (distance between)

17
Q

What is the relationship between attractive force and particle separation (as per potential diagram)?

A
  • Small attractive force exists at big separations

- Very sharp increase in attraction at small separations

18
Q

How is charge distributed around a particle in a colloid in relation to repulsive force?

A
  • Most colloidal particles charged (from ion dissolution/ion adsorption via surfactants)
  • Electrical double layer formed at surface of colloidal particle; Stern layer and Gouy-Chapmanlayer
  • Only so many oppositely charged ions occupy the colloidal layer; repelling like charges
19
Q

What is the stern potential?

A

Potential of absorbed cations on the surface

20
Q

What is the zeta potential?

A

Potential at the end of the stern plane

21
Q

What is the relationship between repulsive force and particle separation (as per potential diagram)?

A
  • Repulsion falls to zero at certain distance quite rapidly; where there still is a weak attractive force
  • Repulsion does not increase sharply at close separations
22
Q

What is happening in a disperse system at the Secondary Minimum?

A
  • Weak attraction

- Causes flocculation (even at large separation distances)

23
Q

What is happening in a disperse system at the Primary Maximum?

A
  • Repulsive barrier to aggregation; repulsion between particles not present until quite close together
  • Results in colloidal stability
24
Q

What is happening in a disperse system at the Primary Minimum?

A
  • Permanent aggregation of particles

- Energy has superseded Primary Maximum overcoming repulsor forces

25
Q

Where does low kinetic energy place a particle in terms of a potential diagram, and what is the end result?

A
  • Primary Maximum too great a barrier
  • Particle has insufficient energy to continue its path towards neighbouring particle
  • Particle also has insufficient energy to escape the Secondary Minimum

RESULT - FLOCCULATION

26
Q

Where does intermediate kinetic energy place a particle in terms of a potential diagram, and what is the end result?

A
  • Primary Maximum too great a barrier
  • Particle has insufficient energy to continue its path towards a neighbouring particle
  • Particle escapes the Secondary Minimum (Brownian Motion)

RESULT - STABLE COLLOIDAL FORMULATION

27
Q

Where does high kinetic energy place a particle in terms of a potential diagram, and what is the end result?

A
  • Primary Maximum is insufficient to stop particle

RESULT - COAGULATION

B32PAI - Pharmaceutics (3 decks)

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